Edgewise Therapeutics, Inc. · NASDAQ:EWTX
Edgewise Therapeutics — Investor Presentation (November 2024)
57 slides from Edgewise Therapeutics's investor presentation, November 2024
Slide 1: Leaders in Muscle Disease Science
Leaders in Muscle Disease Science Corporate Overview November 2024 1
Slide 2: Forward looking statement
Forward looking statement This presentation contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this presentation that are not purely historical are forward-looking statements.
Slide 3: The Evolution of Edgewise
The Evolution of Edgewise Identified a unique EDG-7500 set of CV EDG-7500 enters the clinic; Initiated molecules as part EDG-7500 characterized continued CIRRUS-HCM, of skeletal muscle identified as as a selective research on EDG-7500 counter-screen lead molecule cardiac novel P2 program CV program
Slide 4: Focused on muscle science; rapidly advancing portfolio; patient commitment
Focused on muscle science ● Global leader in muscle disease therapeutic development ● Deep knowledge of integrated muscle physiology ● Novel & holistic therapeutic approach to protect muscle Rapidly advancing portfolio ● Advancing EDG-7500 in oHCM, nHCM, and other potential indications ● Moving seva
Slide 5: Our pipeline
Our pipeline Phase 3/ Preclinical Phase 1 Phase 2 Pivotal Becker muscular dystrophy Dystrophy Muscular Sevasemten Myosin ATPase Duchenne muscular dystrophy Becker / LGMD2i / McArdle EDG-7500 Undisclosed Cardiovascular cardiac Hypertrophic Cardiomyopathy (HCM) sarcomeric target Undisclosed Cardiac sa
Slide 6: Contraction-induced muscle damage & sevasemten
Contraction-induced muscle damage & sevasemten 6
Slide 7: The root driver of disease in muscular dystrophies
The root driver of disease in muscular dystrophies 7
Slide 8: Muscle damage in muscular dystrophies causes leak of injury biomarkers
Muscle damage in muscular dystrophies causes leak of injury biomarkers, including CK, TNNI2 and myoglobin, into the circulation Activity-Induced Muscle Injury in Muscular Dystrophies Contraction induced muscle damage Fast fibers are subsequently injured leading to release of causes excessive degener
Slide 9: Sevasemten: first-in-class fast myofiber myosin inhibitor
Sevasemten: A first-in-class fast myofiber (type II) myosin inhibitor designed to protect against contraction-induced muscle injury Sevasemten Therapeutic Hypothesis Protected sarcomere Sevasemten Prevention of contraction-induced muscle injury Duchenne Excessive contraction induced muscle damage Co
Slide 10: Ongoing sevasemten clinical trials in muscular dystrophy
Ongoing sevasemten clinical trials in muscular dystrophy Ph 2 Becker PK, biomarkers and longer-term safety OLE Fully Enrolled (NCT05291091) Pivotal Becker Cohort Function (NSAA), PK, biomarkers and longer-term safety OLE Recruiting (NCT05291091) Becker Ph 2 Becker, LGMD2i, & McArdle Exercise challen
Slide 11: Sevasemten program in Becker muscular dystrophy
Sevasemten program in Becker muscular dystrophy 11
Slide 12: Our goal is to positively impact the course of Becker muscular dystrophy
Our goal is to positively impact the course of Becker muscular dystrophy ● Becker is a rare, genetic, life-shortening, debilitating and degenerative neuromuscular disorder ● The disease predominately affects males and imposes significant physical, emotional, financial and social impacts on the indiv
Slide 13: Natural history data in Becker: NSAA decline is consistent and predictable
Natural history data in Becker support that functional decline, measured by NSAA, is consistent and predictable Natural history of Becker muscular dystrophy 0 -2 Change in NSAA • NSAA, a multi-item scale, is utilized in muscular dystrophy natural history studies to -4 longitudinally assess functiona
Slide 14: Open-label trial assessing sevasemten safety and PK in Becker
An open-label, single-center trial to assess sevasemten safety and pharmacokinetics in Becker PRIMARY OBJECTIVE KEY INCLUSION CRITERIA PATIENTS ENROLLED 12 Safety & Ambulatory males aged 18 to 55 years with a dystrophin mutation & a Becker phenotype, tolerability not taking corticosteroids, who coul
Slide 15: Becker participants had significant functional impairment at baseline
Becker participants had significant functional impairment & decreased muscle mass at baseline BECKER AGE NORMATIVE CHARACTERISTIC PARTICIPANTS (n=12) VALUES Age (SD) 33 (8) years – Functional Measures (median) Adults with Becker with 10-meter walk/run 8.4 sec < 4 sec similar baseline NSAA scores Ris
Slide 16: Sevasemten remains well-tolerated at all doses
Sevasemten remains well-tolerated at all doses Treatment Emergent AE After One Year After Two Years (seen in >1 subject) • No dose reductions or COVID-19 4 5 adjustments Fall* 3 4 Dizziness 4 4 • No treatment Arthralgia 4 4 discontinuations due to AEs Nasopharyngitis 3 3 • No SAE URI 3 3 Procedural
Slide 17: After 2 years of treatment, NSAA functional scores predominantly stable or improved
After 2 years of treatment with sevasemten, NSAA functional scores predominantly stable or improved Natural history based on data presented by Bello at MDA (2022) and van de Velde NM et. al., Neurology, 2021 Mean ± 95% CI; Abbreviations: NSAA, North Star Ambulatory Assessment Reference: Data on file
Slide 18: Biomarkers of muscle damage show rapid and sustained decreases
Biomarkers of muscle damage show rapid & sustained decreases with sevasemten Fast skeletal muscle Creatine Kinase CK (CK) troponin I (TNNI2) TNNI2 Myoglobin Myoglobin 2000 40 800 Dose: Dose: Dose: 10 15 20 10 mg 10 15 20 10 mg 10 15 20 10 mg (ng/ml) Myoglobin(ng/mL) 1500 30 600 (ng/mL) TNNI2(ng/mL)
Slide 19: Outcomes of the ARCH study informed GRAND CANYON design
Outcomes of the ARCH study informed the design of the GRAND CANYON pivotal cohort Outcomes of the ARCH Study in Becker Pivotal Dose Safety Function Biomarkers Identified Maximal biomarker Demonstration of Stabilization of response at rapid, sustained functional 10 mg dose Well-tolerated & significan
Slide 20: Exercise Challenge Study: significant reductions in muscle damage biomarkers
Exercise Challenge Study: Sevasemten shows significant reductions in biomarkers of muscle damage • A 16-week randomized, double-blind, placebo-controlled Phase 2 study assessing safety, PK and biomarker response to exercise in adults with Becker, LGMD2I or McArdle disease. • Sevasemten was well tole
Slide 21: Phase 2 CANYON trial in adults with Becker
Phase 2 trial in adults with Becker Topline data from CANYON is anticipated in 4Q24 PRIMARY ENDPOINT KEY INCLUSION ENROLLMENT CRITERIA CK at 6, 9 & 12 months Adult individuals with Becker with NSAA 5-32, not on corticosteroids 40 Study design - 12 months 10mg R PO daily Screening 3:1 Placebo Month 0
Slide 22: GRAND CANYON pivotal cohort in Becker
Global, multi-center, placebo-controlled pivotal cohort assessing efficacy & safety of sevasemten in Becker POTENTIAL REGISTRATIONAL COHORT PRIMARY ENDPOINT KEY INCLUSION TARGET ENROLLMENT POWERED AT CRITERIA NSAA at 18 months Adult individuals with Becker with NSAA 5-32, not taking corticosteroids
Slide 23: CANYON has the potential to be a transformative trial for Edgewise
CANYON has the potential to be a transformative trial for Edgewise CANYON data may allow refinement of the statistical analysis plan of the GRAND CANYON pivotal cohort to optimize trial success Topline data anticipated in 4Q24 Positive data* from CANYON may support pathway to explore early approval
Slide 24: We aim to change the lives of individuals with Becker
We aim to change the lives of individuals with Becker NUMBER OF APPROVED AGE AT WHICH BECKER PATIENTS CAN BECOME WHEELCHAIR BECKER THERAPIES ESTABLISHED OR OTHER MOBILITY DEVICE DEPENDENT TREATMENT CENTERS 0 >16 years of age WITH NEUROMUSCULAR SPECIALISTS NUMBER OF BECKER PATIENTS IN US, EU-5 & JAPA
Slide 25: Sevasemten program in Duchenne muscular dystrophy
Sevasemten program in Duchenne muscular dystrophy 25 25
Slide 26: Goal: a new therapeutic approach that could become standard of care in Duchenne
Our goal is to develop a new therapeutic approach that could become the standard of care in Duchenne ● Despite recent advances, the Duchenne community remains in need of new therapeutic options ● Sevasemten mutation-agnostic MOA as potential foundational therapy—alone or in combination ● Edgewise is
Slide 27: Randomized Phase 2 trial of sevasemten followed by an OLE
A randomized, double-blind, placebo-controlled Phase 2 trial of sevasemten, followed by an OLE PATIENTS ENROLLED PRIMARY ENDPOINT NUMBER OF SITES Safety & tolerability >60 boys with Duchenne aged 4-9 years >12 Part A - 12 weeks Sequentially enrolled, placebo-controlled Part B - 21 months dose-escala
Slide 28: Phase 2 study in Duchenne boys previously treated with gene therapy
A Phase 2 study of sevasemten in Duchenne boys previously treated with gene therapy PRIMARY ENDPOINT TARGET ENROLLMENT NUMBER OF SITES Safety & tolerability >24 7 participants aged 6-17 years in the US Part A - 16 weeks Part B - 40 weeks Screening and randomization OLE (may be dose-escalated based o
Slide 29: Trials designed to address all ambulatory boys with Duchenne
Our current clinical trials with sevasemten are designed to address all ambulatory boys living with Duchenne Treated with steroids only Treated with DUCHENNE BOYS other dystrophin / non-dystrophin therapies Sevasemten as potential standard of care Not treated with steroids Treated with a gene therap
Slide 30: Duchenne market has significant growth potential
Duchenne market has significant growth potential, with sevasemten uniquely positioned against the therapeutic backdrop $5 Additional upside** billion NUMBER OF DUCHENNE PATIENTS IN US, EU-5 & JAPAN Molecules with Future US muscle- targeted MOAs that enable expansion into ~35,000 Duchenne other marke
Slide 31: EDG-7500 program in Hypertrophic Cardiomyopathy (HCM)
EDG-7500 program in Hypertrophic Cardiomyopathy (HCM) 31 31
Slide 32: HCM: chronic, progressive and the most commonly inherited heart disease
Hypertrophic cardiomyopathy (HCM): Chronic, progressive & the most commonly inherited heart disease ● HCM impacts ~1 in 200-500 people in the US − Diagnosis at any age; mid-40s most common − Characterized by diastolic dysfunction, left ventricular outflow tract obstruction (LVOTO), & atrial & ventri
Slide 33: HCM: abnormalities in heart muscle structure and function
HCM: Abnormalities in heart muscle structure & function lead to severe abnormalities in cardiac performance HEALTHY HEART OBSTRUCTIVE HCM NON-OBSTRUCTIVE HCM (~65% OF PATIENT POPULATION) (~35% OF PATIENT POPULATION) Normal contraction Excessive contraction & impaired relaxation 33
Slide 34: Treatments for HCM have key limitations
Treatments for HCM have key limitations leaving substantial unmet needs for patients LIMITED BENEFIT ACROSS THE SUBOPTIMAL PATIENT RISK OF HEART FAILURE1,2 SPECTRUM OF HCM EXPERIENCE Efficacy and safety Safety-driven frequent Mavacamten black box limitations with echo monitoring1-3 warning for HF3 i
Slide 35: EDG-7500: slows acto-myosin engagement and speeds disengagement
EDG-7500: Designed to Slow Rate of Acto-Myosin Engagement and Speed Disengagement Without Inactivating Myosin Heads The Sarcomere is the Molecular Unit in Cardiac Muscle Responsible for Heart Contraction and Relaxation Gene # of mutations to TNNI3 Protein Symbol cause HCM TNNT2 Cardiac -MyHC MYH7 1
Slide 36: A compelling preclinical package supported clinical studies of EDG-7500
A compelling preclinical package supported initiation of clinical studies of EDG-7500 as a novel therapy for HCM Preclinical model Key result Preserves myosin head motor function In vitro: Myofibril systems1 More potent at low calcium In vivo: MYBPC3 A31P feline validated Potent LVOT gradient reduct
Slide 37: EDG-7500 is positioned to address unmet needs in HCM
EDG-7500 is positioned to address unmet needs in HCM Targeted MOA* Minimal changes Potential ease of in LVEF* administration EDG-7500 is targeted to EDG-7500 avoids EDG-7500’s novel MOA address both obstructive excessive drops in supports investigating and non-obstructive HCM systolic performance fi
Slide 38: EDG-7500 Phase 1 Trial in Healthy Subjects
EDG-7500 Phase 1 Trial in Healthy Subjects 38
Slide 39: Study overview of EDG-7500 in healthy adults
Study overview of EDG-7500 in healthy adults PRIMARY OBJECTIVE KEY INCLUSION CRITERIA ENROLLMENT KEY OUTCOME MEASURES 72 Safety & tolerability in Healthy male, PK, LVEF healthy subjects non-pregnant female 18 to <60 years of age Part A (n=48) Single Ascending Dose (SAD) 5 mg 15 mg 50 mg 100 mg 200 m
Slide 40: EDG-7500 well tolerated across all doses in SAD and MAD cohorts
EDG-7500 was well tolerated across all doses in both the SAD & MAD healthy subject cohorts (continued) Across both the SAD and MAD cohorts: • No significant changes in vital signs were observed • Well-tolerated with no clinically significant changes or trends in clinical chemistry, hematology, or EC
Slide 41: Steady-state achieved ~4 days after start of once-daily dosing
Steady-state was achieved ~4 days after start of once-daily dosing with EDG-7500 Plasma Concentration Over Time (mean ± SD) After 3 Ascending Doses of Daily EDG-7500 for 14 Days Concentration (ng/mL) 400 300 EDG-7500 Plasma 200 100 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Days Post-Dose 25 mg QD 50 mg Q
Slide 42: No change in contractility versus placebo with increasing doses
There was no change in contractility versus placebo & baseline with increasing doses of EDG-7500 20 SAD MAD Placebo (N=12) EDG-7500 (N=36) Placebo (N=6) EDG-7500 (N=18) Mean Baseline LVEF (SD) 63.7 (2.0) 61.4 (3.7) 60.9 (2.3) 61.2 (2.2) 10 from Baseline (%) LVEF Change 0 -10 -20 -30 Pooled Placebo P
Slide 43: Observations highlight a potentially unique mechanism to target HCM
Observations with EDG-7500 highlight a potentially unique mechanism to target HCM without risk of reducing LVEF • EDG-7500 was well-tolerated with no clinically significant changes or trends in clinical chemistry, hematology or ECGs • EDG-7500 showed optimal PK properties supporting once-daily fixed
Slide 44: Phase 2 CIRRUS-HCM Trial in oHCM
Phase 2 CIRRUS-HCM Trial in oHCM 44
Slide 45: Topline data: CIRRUS part A cohort of oHCM patients
Topline data: CIRRUS part A cohort of oHCM patients treated with a single dose of EDG-7500 PRIMARY OBJECTIVE KEY INCLUSION CRITERIA ENROLLMENT KEY OUTCOME MEASURES Safety & tolerability in • Healthy male, non-pregnant female ≥ 18 diagnosed with oHCM • Safety and tolerability 11 adults with oHCM • Re
Slide 46: Pre-specified efficacy evaluable population
Pre-specified efficacy evaluable population • 11 patients were eligible at screening and constituted the safety population • 7 patients met the following criteria at baseline qualifying for efficacy evaluation: – Resting left ventricular outflow tract gradient (LVOT-G) ≥ 30 mmHg and Valsalva LVOT-G
Slide 47: CIRRUS-HCM Part A: Baseline patient demographics and characteristics
CIRRUS-HCM Part A: Baseline oHCM Patient Demographics and Characteristics CHARACTERISTIC oHCM PARTICIPANTS (n=11) Age (Years), Mean (SD) 59 (15) Sex – Female (%) 73 Race – Black/White (%) 9 / 91 BMI (kg/m2) 28 (4) NYHA Class (%) Class I 27 Class II 45 Class III 27 Time from HCM Diagnosis (years), Me
Slide 48: Single doses of EDG-7500 well tolerated in oHCM
Single doses of EDG-7500 were well tolerated across all 3 doses studied in oHCM patients • EDG-7500 was well-tolerated by all oHCM patients • No treatment emergent abnormalities in clinical hematology or chemistry laboratories • No patients experienced a decrease in LVEF <50% Summary of AEs Dose Ter
Slide 49: Significant reductions of Resting and Valsalva LVOT-G
EDG-7500 led to significant reductions of Resting and Valsalva LVOT-G in the combined 100/200 mg cohorts Reduction in Resting LVOT-G of 67% Reduction in Valsalva LVOT-G of 55% 50 mg (n=2) 100 mg (n=3) 200mg (n=2) 3 of 5 Patients (100 mg and 200 mg Cohorts) Had a Resting LVOT-G of <30 mmHg & a Valsal
Slide 50: Gradient relief achieved without meaningful reduction in LVEF
Gradient relief in oHCM patients was achieved without a meaningful reduction in LVEF Group Mean Values (n=11) 80 -0.2% +2.4% 70 -2.0% +0.8% -3.2% -1.2% 60 50 LVEF (%) Safety threshold 40 30 20 10 50 mg (n=3) 100 mg (n=4) 200mg (n=4) 0 Pre 2 hr. 24 hr. There was no correlation between EDG-7500 plasma
Slide 51: Robust reductions in NT-proBNP
EDG-7500 administration resulted in robust reductions in NT-proBNP, a key marker of heart failure in HCM1 Mean Relative Change from Baseline (n=7)* 10 Relative Change from Baseline (%) 0 -10 -17% -20 NTpro-BNP -30 -31% -40 -50 Baseline NT-proBNP levels ranged from 279-11,408 pg/ml for the efficacy e
Slide 52: EDG-7500 relieved LVOT-G without reductions in LVEF
EDG-7500 in oHCM patients relieved LVOT-G without reductions in LVEF • EDG-7500 administration was well tolerated across all doses studied in oHCM patients • EDG-7500 administration led to a reduction in resting LVOT-G of 67% for the 100/200 mg cohorts combined with multiple individuals achieving gr
Slide 53: Positive part A data supported initiation of parts B and C
Positive data from CIRRUS-HCM part A supported the initiation of parts B and C in oHCM and nHCM, respectively • Edgewise initiated enrollment of patients in the 28 Day study of EDG-7500 for both obstructive and non-obstructive HCM • Part B: designed to demonstrate continued safety and deepening of e
Slide 54: CIRRUS-HCM: Clinical Trial Design
CIRRUS-HCM: Clinical Trial Design PRIMARY OBJECTIVE KEY INCLUSION CRITERIA TARGET ENROLLMENT KEY OUTCOME MEASURES ~50 Safety & tolerability Male and female patients Cardiovascular PD, LVEF, in adults with HCM ≥ 18 years of age with HCM Biomarkers, PK LVEF ≥ 60% PART A: Single Dose (11 oHCM patients)
Slide 55: Aspirational target product profile for EDG-7500 in HCM
Aspirational target product profile for EDG-7500 in the treatment of HCM Based on observations to date, no concerns Safety of LVEF drops Ability to deepen functional, symptom and QoL Efficacy improvements without concerns of LVEF drops < 50% No excessive monitoring requirements outside of Monitoring
Slide 56: Edgewise upcoming value-generating milestones
Edgewise upcoming value-generating milestones H1 2024 H2 2024 H1 2025 Phase 2 CIRRUS-HCM Phase 1/Phase 2 Initiation ✓ EDG-7500 data in HVs & oHCM** ✓ Cardiac Hypertrophic Cardiomyopathy EDG-7500 Phase 2 28-day study Phase 2 28-day study Initiate in oHCM & nHCM** ✓ Initial Data readout Becker ARCH ✓
Slide 57: Well-capitalized to execute important milestones
Well-capitalized to execute important milestones across both EDG-7500 & sevasemten CASH, CASH EQUIVALENTS & DEBT (1) COMMON (1) SHARES OUTSTANDING MARKETABLE SECURITIES (NASDAQ: EWTX) ~$493M $0 ~94M CASH RUNWAY THROUGH 2027 As of September 30, 2024 57
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